Back to resultsDay-Night Rhythm in Human Skeletal Muscle
Primary Purpose
Diabetes Mellitus, Type 2, Insulin Resistance
Status
Completed
Phase
Not Applicable
Locations
Netherlands
Study Type
Interventional
Intervention
Standardized living protocol
Sponsored by
About this trial
This is an interventional basic science trial for Diabetes Mellitus, Type 2 focused on measuring Circadian Rhythm
Eligibility Criteria
Inclusion Criteria:
- Caucasian
- Healthy (as determined by dependent physician based on medical questionnaire)
- Male
- Age: 18-35 years
- Normal BMI (18-25 kg/m2)
- Regular sleeping time (normally 7-9h daily)
Exclusion Criteria:
- Extreme early bird or extreme night person (score ≤30 or ≥70 on MEQ-SA questionnaire)
- Heavily varying sleep-wake rhythm
- Shiftwork during last 3 months
- Travel across >1 time zone in the last 3 months
- Engagement in exercise > 2 hours total per week
- Using >400mg caffeine daily
- Smoking
- Unstable body weight (weight gain or loss > 3kg in the last 3 months)
- Significant food allergies/intolerance (seriously hampering study meals)
- Participation in another biomedical study within 1 month before the first study visit
- Any contra-indication to Magnetic Resonance Imaging (MRI) scanning
Sites / Locations
- Maastricht University
Arms of the Study
Arm 1
Arm Type
Other
Arm Label
Standardized living protocol
Arm Description
Subjects are kept at the research facility to adhere to a standardized living protocol, mimicking a normal daily living situation. During the study, multiple tests will be performed, including muscle biopsies, blood draws, MRS measurements and indirect calorimetry.
Outcomes
Primary Outcome Measures
Day-night rhythm in skeletal muscle mitochondrial respiration
O2-flux (pmol/mg/s) measured with high resolution respirometry upon administration of different substrates
Secondary Outcome Measures
Day-night rhythm in whole-body energy metabolism
Energy expenditure (kJ/min), glucose oxidation (g/min) and fat oxidation (g/min) measured by indirect calorimetry
Day-night rhythm in muscle DNA, mRNA and protein levels of markers involved in molecular clock and mitochondrial metabolism.
Quantify mRNA and protein levels by qPCR or micro-array and Western blots
Day-night rhythm of in markers of normal day-night rhythm (cortisol, melatonin, core body temperature)
Blood cortisol and melatonin levels and core body temperature measured by an ingested telemetric pill.
Day-night rhythm in blood metabolic compounds (e.g. glucose, insulin, FFA's, cholesterol)
Day-night rhythm of molecular clock mRNA and protein levels in blood PBMC's
Measured by qPCR and Western Blots
Change in liver volume and liver lipid concentration during the day
Measured by Magnetic Resonance Imaging and -Spectroscopy (MRI/MRS). Lipid signals in the MRS spectra will be quantified while suppressing the strong water signal in the region of interest (right liver lobe)
Full Information
NCT ID
NCT02261168
First Posted
September 24, 2014
Last Updated
September 4, 2015
Sponsor
Maastricht University Medical Center
1. Study Identification
Unique Protocol Identification Number
NCT02261168
Brief Title
Day-Night Rhythm in Human Skeletal Muscle
Official Title
Day-night Rhythm in Human Skeletal Muscle Metabolism
Study Type
Interventional
2. Study Status
Record Verification Date
September 2015
Overall Recruitment Status
Completed
Study Start Date
November 2014 (undefined)
Primary Completion Date
July 2015 (Actual)
Study Completion Date
July 2015 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Maastricht University Medical Center
4. Oversight
Data Monitoring Committee
No
5. Study Description
Brief Summary
This study evaluates the existence of a day-night rhythm in skeletal muscle energy metabolism in healthy lean subjects. Subjects will stay at the research facility for 44 hours with a standardized living protocol during which several measurements of skeletal muscle and whole body energy metabolism will be performed.
Detailed Description
Recent evidence from both observational and experimental studies indicates that disobeying our normal day-night rhythm negatively influences our metabolic and cardiovascular health, possibly leading to obesity and type 2 diabetes mellitus (T2DM). An important hallmark of obesity and T2DM is a decreased skeletal muscle mitochondrial function. Interestingly, recent research indicates that also skeletal muscle mitochondrial function under the influence of a day-night rhythm. The main objective of this study is to investigate the presence of a day-night rhythm in skeletal muscle energy metabolism (in particular mitochondrial function) of healthy young participants. Therefore, subjects will stay at the research unit for 44 hours, with standardized meals and sleeping time. During this period we will take five muscle biopsies, perform indirect calorimetry measurements and blood draws.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Diabetes Mellitus, Type 2, Insulin Resistance
Keywords
Circadian Rhythm
7. Study Design
Primary Purpose
Basic Science
Study Phase
Not Applicable
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
12 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Standardized living protocol
Arm Type
Other
Arm Description
Subjects are kept at the research facility to adhere to a standardized living protocol, mimicking a normal daily living situation. During the study, multiple tests will be performed, including muscle biopsies, blood draws, MRS measurements and indirect calorimetry.
Intervention Type
Other
Intervention Name(s)
Standardized living protocol
Intervention Description
Subjects stay at the research facility for 44 hours and adhere to a standard sleeping, eating and activity protocol. During this protocol, multiple measurements will be performed including skeletal muscle biopsies (m. vastus lateralis), blood draws, indirect calorimetry and MRS measurements.
Primary Outcome Measure Information:
Title
Day-night rhythm in skeletal muscle mitochondrial respiration
Description
O2-flux (pmol/mg/s) measured with high resolution respirometry upon administration of different substrates
Time Frame
40 hours.
Secondary Outcome Measure Information:
Title
Day-night rhythm in whole-body energy metabolism
Description
Energy expenditure (kJ/min), glucose oxidation (g/min) and fat oxidation (g/min) measured by indirect calorimetry
Time Frame
40 hours.
Title
Day-night rhythm in muscle DNA, mRNA and protein levels of markers involved in molecular clock and mitochondrial metabolism.
Description
Quantify mRNA and protein levels by qPCR or micro-array and Western blots
Time Frame
40 hours.
Title
Day-night rhythm of in markers of normal day-night rhythm (cortisol, melatonin, core body temperature)
Description
Blood cortisol and melatonin levels and core body temperature measured by an ingested telemetric pill.
Time Frame
measured during the 2nd study day
Title
Day-night rhythm in blood metabolic compounds (e.g. glucose, insulin, FFA's, cholesterol)
Time Frame
measured during the 2nd study day
Title
Day-night rhythm of molecular clock mRNA and protein levels in blood PBMC's
Description
Measured by qPCR and Western Blots
Time Frame
measured during the 2nd study day
Title
Change in liver volume and liver lipid concentration during the day
Description
Measured by Magnetic Resonance Imaging and -Spectroscopy (MRI/MRS). Lipid signals in the MRS spectra will be quantified while suppressing the strong water signal in the region of interest (right liver lobe)
Time Frame
First study day 6 PM, second study day 7 AM
10. Eligibility
Sex
Male
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
35 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
Inclusion Criteria:
Caucasian
Healthy (as determined by dependent physician based on medical questionnaire)
Male
Age: 18-35 years
Normal BMI (18-25 kg/m2)
Regular sleeping time (normally 7-9h daily)
Exclusion Criteria:
Extreme early bird or extreme night person (score ≤30 or ≥70 on MEQ-SA questionnaire)
Heavily varying sleep-wake rhythm
Shiftwork during last 3 months
Travel across >1 time zone in the last 3 months
Engagement in exercise > 2 hours total per week
Using >400mg caffeine daily
Smoking
Unstable body weight (weight gain or loss > 3kg in the last 3 months)
Significant food allergies/intolerance (seriously hampering study meals)
Participation in another biomedical study within 1 month before the first study visit
Any contra-indication to Magnetic Resonance Imaging (MRI) scanning
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Patrick Schrauwen, PhD
Organizational Affiliation
Professor
Official's Role
Principal Investigator
Facility Information:
Facility Name
Maastricht University
City
Maastricht
Country
Netherlands
12. IPD Sharing Statement
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Day-Night Rhythm in Human Skeletal Muscle
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